Hyperfunction of Muscarinic Receptor Maintains Long-Term Memory in 5-HT4 Receptor Knock-Out Mice

Luis Segu, Marie-José Lecomte, Mathieu Wolff, Julie Santamaria, René Hen, Aline Dumuis, Sylvie Berrard, Joël Bockaert, Marie-Christine Buhot, Valérie Compan
PLoS ONE. 2010-03-04; 5(3): e9529
DOI: 10.1371/journal.pone.0009529

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1. PLoS One. 2010 Mar 4;5(3):e9529. doi: 10.1371/journal.pone.0009529.

Hyperfunction of muscarinic receptor maintains long-term memory in 5-HT4 receptor
knock-out mice.

Segu L(1), Lecomte MJ, Wolff M, Santamaria J, Hen R, Dumuis A, Berrard S,
Bockaert J, Buhot MC, Compan V.

Author information:
(1)Centre de Neurosciences Intégratives et Cognitives, CNRS UMR5228, Bordeaux
University, Talence, France.

Patients suffering from dementia of Alzheimer’s type express less serotonin 4
receptors (5-HTR(4)), but whether an absence of these receptors modifies learning
and memory is unexplored. In the spatial version of the Morris water maze, we
show that 5-HTR(4) knock-out (KO) and wild-type (WT) mice performed similarly for
spatial learning, short- and long-term retention. Since 5-HTR(4) control mnesic
abilities, we tested whether cholinergic system had circumvented the absence of
5-HTR(4). Inactivating muscarinic receptor with scopolamine, at an ineffective
dose (0.8 mg/kg) to alter memory in WT mice, decreased long-term but not
short-term memory of 5-HTR(4) KO mice. Other changes included decreases in the
activity of choline acetyltransferase (ChAT), the required enzyme for
acetylcholine synthesis, in the septum and the dorsal hippocampus in 5-HTR(4) KO
under baseline conditions. Training- and scopolamine-induced increase and
decrease, respectively in ChAT activity in the septum in WT mice were not
detected in the 5-HTR(4) KO animals. Findings suggest that adaptive changes in
cholinergic systems may circumvent the absence of 5-HTR(4) to maintain long-term
memory under baseline conditions. In contrast, despite adaptive mechanisms, the
absence of 5-HTR(4) aggravates scopolamine-induced memory impairments. The
mechanisms whereby 5-HTR(4) mediate a tonic influence on ChAT activity and
muscarinic receptors remain to be determined.

DOI: 10.1371/journal.pone.0009529
PMCID: PMC2832007
PMID: 20209108 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus